Hepatocellular Carcinoma (HCC)Phase 2LEAF-01NCT07047586
Lenvatinib Plus Tislelizumab Versus Lenvatinib Alone in Hepatocellular Carcinoma Previously Treated With Anti-PD1/PD-L1 and Bevacizumab
A Phase 2 study testing Tislelizumab and Lenvatinib in people with Hepatocellular Carcinoma (HCC), run by Fudan University at 1 site in China.
Trial summary
To evaluate the efficacy and safety of lenvatinib plus tislelizumab versus lenvatinib alone for patients with advanced hepatocellular carcinoma (HCC) who have progressed on prior systemic treatment with Anti-PD1/PD-L1 plus bevacizumab combination. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Tislelizumab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 1 siteChina
- Study dates
- 2 Jul 2025to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained.
- Age ≥ 18 years at time of study entry.
- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
- Disease progression following prior anti-PD1/PD-L1 plus bevacizumab combination treatment for HCC.
- At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
- Child-Pugh scores 5-7, performance status (PS) ≤ 2 (ECOG scale).
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- Subjects with chronic HBV infection must have HBV DNA viral load < 100 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy.
- Life expectancy of at least 12 weeks.
- Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥60 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula)
- Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.
Who cannot join
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Patients on a liver transplantation list or with advanced liver disease.
- History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
- Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
- Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
- Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
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- Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
- Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to: a) history of interstitial lung disease b) Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) c) known acute or chronic pancreatitis d) active tuberculosis e) any other active infection (viral, fungal or bacterial) requiring systemic therapy f) history of allogeneic tissue/solid organ transplant g) diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment. h) Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. i) Live vaccine within 30 days prior to the first dose of treatment or during study treatment. j) History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS.
- Medication that is known to interfere with any of the agents applied in the trial.
- Any other efficacious cancer treatment except protocol specified treatment at study start.
- Patient has received any other investigational product within 28 days of study entry.
- Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200032
Peng Wang, MD, +86021-64041990, peng_wang@fudan.edu.cn
Peng Wang, MD
About this study
Official title: Lenvatinib Plus Tislelizumab Versus Lenvatinib Alone in Hepatocellular Carcinoma Previously Treated With Anti-PD1/PD-L1 and Bevacizumab: a Multicenter, Randomized, Phase 2 Study
To evaluate the efficacy and safety of lenvatinib plus tislelizumab versus lenvatinib alone for patients with advanced hepatocellular carcinoma (HCC) who have progressed on prior systemic treatment with Anti-PD1/PD-L1 plus bevacizumab combination.
Read the detailed description
This is a phase 2, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of lenvatinib plus tislelizumab versus lenvatinib alone in participants with advanced hepatocellular carcinoma (HCC) who have progressed on prior systemic treatment with Anti-PD1/PD-L1 plus bevacizumab combination.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Tislelizumab, Lenvatinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
Tislelizumab will be administered by IV, 200 mg on day 1 of each 21 day cycle until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
LenvatinibDrug
Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib+ tislelizumab | Experimental | Not described Receives: Drug: Tislelizumab; Drug: Lenvatinib |
| Lenvatinib | Active comparator | Not described Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
Measured: max 24 months
Secondary outcomes (7)
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
Measured: max 24 months
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD).
Measured: max 24 months
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Measured: max 24 months
Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
TTR is defined as the time from the start of treatment until the first objective observation of a response (either partial response, PR, or complete response, CR), provided that the response is subsequently confirmed
Measured: max 24 months
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death.
Measured: max 42 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
Measured: max 42 months
Translational study
Proportion of different immune cell types in tumors based on single-cell RNA sequencing between responders and non-responders.
Measured: max 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2025
- Study start2 Jul 2025
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peng Wang, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07047586
- Sponsor's protocol ID
- LEAF-01
- Acronym
- LEAF-01
- Status last verified
- Jul 2025
- First submitted
- 24 Jun 2025
- Last updated
- 3 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenvatinib Plus Tislelizumab Versus Lenvatinib Alone in Hepatocellular Carcinoma Previously Treated With Anti-PD1/PD-L1 and Bevacizumab: a Multicenter, Randomized, Phase 2 Study
- ClinicalTrials.gov ID
- NCT07047586
- Acronym / sponsor ID
- LEAF-01 / LEAF-01
- Conditions
- Hepatocellular Carcinoma (HCC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 2 Jul 2025 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 2 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy and safety of lenvatinib plus tislelizumab versus lenvatinib alone for patients with advanced hepatocellular carcinoma (HCC) who have progressed on prior systemic treatment with Anti-PD1/PD-L1 plus bevacizumab combination.
Detailed description
This is a phase 2, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of lenvatinib plus tislelizumab versus lenvatinib alone in participants with advanced hepatocellular carcinoma (HCC) who have progressed on prior systemic treatment with Anti-PD1/PD-L1 plus bevacizumab combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib+ tislelizumab | Experimental | Drug: Tislelizumab, Drug: Lenvatinib |
| Lenvatinib | Active comparator | Drug: Lenvatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent obtained.
- Age ≥ 18 years at time of study entry.
- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
- Disease progression following prior anti-PD1/PD-L1 plus bevacizumab combination treatment for HCC.
- At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
Key exclusion criteria (13 listed)
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Patients on a liver transplantation list or with advanced liver disease.
- History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
- Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
- Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TislelizumabTislelizumab will be administered by IV, 200 mg on day 1 of each 21 day cycle until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. | Drug | Lenvatinib+ tislelizumab |
| LenvatinibLenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. | Drug | Lenvatinib, Lenvatinib+ tislelizumab |
Primary outcome
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
7 secondary outcomes
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 42 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: max 42 months
Translational study
Time frame: max 42 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab and Lenvatinib in people with Hepatocellular Carcinoma (HCC), run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Peng Wang, MD (86-21-64041990, peng_wang@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (time frame: max 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.